Tryptophan is an essential amino acid found in numerous naturally occurring plant proteins and which has a number of interesting medicinal qualities including treatment of insomnia as well as an adjunct in the treatment of a number of psychiatric disorders. After absorption, tryptophan circulates in the blood as approximately 80% bound to plasma albumin with the remaining 20% circulating as free tryptophan, and under appropriate conditions, tryptophan is transported into the brain. Once across the blood brain (BBB), tryptophan becomes available for metabolism into serotonin, a neurotransmitter implicated in mood and sleep regulation (Boman, 1988).
Subsequently, and, somewhat controversially, in anxiety as well (review—Young 1986). Some studies suggest that tryptophan is of benefit to those that suffer from anxiety states but this finding has not been borne out in a consistent fashion (Pecknold et al., 1982).
Subsequently, serotonin, in turn, is metabolized to melatonin; a sleep related hormone found in the pineal gland, a small cone-like structure in the epithalamus of the brain that regulates the 24-hour circadian rhythm in humans. Ingestion of a sufficient quantity of tryptophan per se consistently results in reduced sleep latency i.e. the time from “lights out” to sleep, and an improvement in overall quality of sleep through improved sleep architecture (Boman, 1988). Tryptophan metabolism to serotonin also serves well in conditions where depleted serotonin levels exists such as anxiety disorders, depression, obsessive-compulsive some pain disorders, aggression and eating disorders.
The hypnotic effects of tryptophan are well studied and follow a fairly flat dose-response curve with a plateau at approximately 1000 mg (for review see Schneider-Helmut and Spinweber, 1986). When given alone, as little as 250 mg of tryptophan is sufficient to produce improved sleep in people with mild insomnia, or in those reporting longer-than-average sleep latency (Hartmann and Spinweber, 1976; Hartmann 1982). Dosages of 1000 mg are associated with more consistent results (Schneider-Helmut and Spinweber, 1986) but higher dosages (2,000-12,000 mg) offer little extra benefit and, indeed, the highest dosages (12,000 mg) are associated with disrupted sleep architecture despite a reduction in sleep latency (Griffiths et al 1972).
The dosage of tryptophan used to treat anxiety states varies from approximately 3 g to 8 g per day (Pecknold et al 1982). Literature reviews consistently emphasize the distinction between the administration of “free” tryptophan and protein-bound tryptophan. Tryptophan is the least abundant amino acid in proteins. Competition from other large neutral amino acids (LNAAs) for transport sites into the brain thereby prevents any rise in brain tryptophan levels after ingestion of a meal containing protein (Young 2002).
There remains a need, however, for addressing the aforesaid medical conditions without administration of “free” tryptophan per se.